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dc.contributor.author
Beusch, Irene
dc.contributor.author
Barraud, Pierre
dc.contributor.author
Moursy, Ahmed
dc.contributor.author
Clery, Antoine
dc.contributor.author
Allain, Frédéric H.-T.
dc.date.accessioned
2018-01-10T15:04:09Z
dc.date.available
2018-01-10T15:04:09Z
dc.date.available
2017-08-08T09:51:07Z
dc.date.available
2017-08-09T11:59:22Z
dc.date.issued
2017
dc.identifier.other
10.7554/elife.25736
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/227323
dc.identifier.doi
10.3929/ethz-b-000175190
dc.description.abstract
HnRNP A1 regulates many alternative splicing events by the recognition of splicing silencer elements. Here, we provide the solution structures of its two RNA recognition motifs (RRMs) in complex with short RNA. In addition, we show by NMR that both RRMs of hnRNP A1 can bind simultaneously to a single bipartite motif of the human intronic splicing silencer ISS-N1, which controls survival of motor neuron exon 7 splicing. RRM2 binds to the upstream motif and RRM1 to the downstream motif. Combining the insights from the structure with in cell splicing assays we show that the architecture and organization of the two RRMs is essential to hnRNP A1 function. The disruption of the inter-RRM interaction or the loss of RNA binding capacity of either RRM impairs splicing repression by hnRNP A1. Furthermore, both binding sites within the ISS-N1 are important for splicing repression and their contributions are cumulative rather than synergistic.
en_US
dc.language.iso
en
en_US
dc.publisher
eLife Sciences Organisation
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.title
Tandem hnRNP A1 RNA recognition motifs act in concert to repress the splicing of survival motor neuron exon 7
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2017-06-26
ethz.journal.title
eLife
ethz.journal.volume
6
en_US
ethz.pages.start
e25736
en_US
ethz.size
35 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
Cambridge
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02521 - Inst. f. Molekularbiologie u. Biophysik / Inst. Molecular Biology and Biophysics::03591 - Allain, Frédéric / Allain, Frédéric
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02521 - Inst. f. Molekularbiologie u. Biophysik / Inst. Molecular Biology and Biophysics::03591 - Allain, Frédéric / Allain, Frédéric
en_US
ethz.date.deposited
2017-08-08T09:51:09Z
ethz.source
FORM
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2018-01-10T16:20:02Z
ethz.rosetta.lastUpdated
2018-12-02T08:43:55Z
ethz.rosetta.exportRequired
true
ethz.rosetta.versionExported
true
dc.identifier.olduri
http://hdl.handle.net/20.500.11850/227283
dc.identifier.olduri
http://hdl.handle.net/20.500.11850/175190
ethz.COinS
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